Oral squamous carcinomas (SCCs) account for 4% of all new cancers and about 2% of cancer deaths annually in the U.S. These cancers affect speech, swallowing, cosmetic appearance, and factors that detract from the quality of life. Despite advances in therapy, no significant improvement in oral cancer survival has occurred in the past 30 years. Progress towards reducing the incidence, morbidity, and mortality of oral SCCs will require a three-tiered approach: identification of the molecular factors that contribute to the initiation and progression, elucidation of the host and tumor characteristics associated with the progression and the development of novel approaches for the treatment of premalignant and microinvasive oral SCCs. Because of its location and extensive referral pattern, the University of Texas M.D. Anderson Cancer Center treats a large number of patients throughout the spectrum of oral SCCs, including oral premalignancies, early stage and advanced stage SCCs. The specific aims of this Center are to: (1) develop an understanding of the molecular events leading to the initiation of oral SCCs; (2) ascertain the contribution of genetic mutations and the induction of degradative enzymes in the early invasion of oral SCCs; (3) develop novel biologic and molecular therapeutic intervention strategies for premalignant and microinvasive oral SCCs; (4) develop effective educational programs for screening and community awareness of prevention strategies for oral cancers. These goals will be addressed by 14 key investigators in basic science, pathology, and transitional clinical investigations. The work to be undertaken includes: (1) molecular markers for diagnostic and biological assessment of premalignancy of oral SCCs; (2) degradative enzymes in microinvasive and early invasive SCC; (3) modulation of cell differentiation, growth, and apoptosis in premalignant and microinvasive oral SCCs, and (4) apoptosis-inducing gene therapy for oral premalignancies. Additionally, two developmental projects will investigate inherited errors in carcinogen metabolism and tissue fluorescence as a non-interventional screening diagnostic tool in early oral SCCs. These studies will be coordinated and supported by three cores devoted to oral cancer research, administration and education; tissue procurement, maintenance, processing, and distribution of clinical samples; and, biostatistical analysis and integration of laboratory, clinical and epidemiological data. These efforts will be supported by program advisers composing an Internal Advisory Committee and an External Advisory Committee. The Oral Cancer Research Center will thus provide new information on the etiology, biology, initiation, progression and treatment of oral SCCs.